Are the Renal and Peritoneal Contributions to Solute and Fluid Removal Equivalent

The KDOQI guidelines and most similar guidelines for PD adequacy quantitate the described dose as weekly total Kt/V or weekly total creatinine clearance (Ccr).  This method of bundling peritoneal and renal clearances assumes that both entities are equivalent. A review of the literature, however, suggests the contrary—peritoneal function is not equivalent to renal function.

In 1995, Maiorca et al. showed that the persistence of RRF conferred a survival advantage to PD patients (1).  In a large, cross-sectional study Diaz-Buxo et al. demonstrated that RRF was strongly correlated with survival and that peritoneal clearance, determined by creatinine clearance, was not (2) (Table I).  Two likely explanations were offered for this finding:

1) The relatively narrow range of peritoneal dialysis dose did not provide sufficient variation to affect survival rates; and,

2) The possibility that the impact of RRF is so much greater than peritoneal dialysis dose, that its presence may obliterate the effect of peritoneal clearance on survival.

Table I.  Association of renal and peritoneal creatinine clearance (Ccr) with odds of death using three logistic models (2). Kp: peritoneal clearance of urea; Kr: renal clearance of urea.

Cp (n=673)

Cr (n=559)

Cpr (n=443)

Variable

X2

p

OR

X2

p

OR

X2

p

OR

Age

30.2

<.001

1.046

26.8

<.001

1.054

13.2

<.001

1.042

Sex (M)

1.7

ns

0.750

2.1

ns

0.691

1.7

ns

0.689

Race (nW)

2.5

ns

1.512

3.8

.050

1.833

2.8

.092

1.881

Diabetes (no)

11.0

<.001

2.023

12.0

<.001

2.431

14.4

<.001

2.991

Kp (L/wk)

1.0

ns

1.009

0.5

ns

1.008

Kr (L/wk)

12.7

<.001

0.876

8.9

0.003

0.887

Several other studies have shown a significant correlation between RRF and survival for both PD (2-6) and HD (7, 8).  Table II summarizes the relative contribution of RRF to PD survival.

Table II.  Relative contribution of residual renal function to survival in peritoneal dialysis

Reference

Year

N

1 mL/min

Risk Reduction (%)

(Reduction in RR)

Diaz-Buxo et al. (2)

1999

2686

Ccr

12

Szeto et al (3)

2000

270

GFR

35

Rocco et al (4)

2000

1512

Ccr

40

Bargman et al (5)

2001

601

GFR

12

Temorshuizen et al (6)

2003

413

GFR

12

Szeto et al. also showed that the peritoneal component of Kt/V or Ccr had no independent effect on any outcome parameter, but the residual renal component strongly correlated with patient outcome (3).  Similarly, Rocco et al. used separate variables for the renal and peritoneal components of dialysis adequacy and found a decreased risk of death for both renal Ccr and Kt/V, but not for the peritoneal components (4).  Data from the CANUSA study was re-analyzed by Bargman et al. to address this issue.  Once again they found a correlation between RRF and survival, but found no association with peritoneal clearance (5).  The authors concluded that the most likely reason for the stronger association of renal function with patient survival was better renal clearance of higher molecular weight solutes when compared to peritoneal clearance.  Similarly, network registry data from the US and the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) confirmed the important contribution of RRF to the overall survival of HD patients (7, 8).

The PD studies attest to the fact that the peritoneal and renal components of clearance are not equivalent.  Therefore, we should raise the question – Is the contribution of peritoneal clearance important?  Obviously, the contribution of peritoneal clearance is clinically significant since anuric patients die within a very short period of time without dialysis and survive for up to many years on peritoneal dialysis.  Szeto et al. studied 140 anuric patients and found that even when there was no RRF, higher dialysis dosage was associated with better actuarial patient survival, better technique survival and shorter hospitalizations (9).  They also pointed out that while both clinical impression and retrospective data suggest that renal and peritoneal clearances are not equivalent, their data strongly support that with progressive loss of RRF, an increase in PD dose can lead to better clinical outcomes.  In view of previous observations suggesting the greater impact of RRF when compared to PD dose, it seems reasonable to intensify PD dose as renal function is lost.

Based on these findings, the following recommendations are well justified:

  1. In the assessment of adequacy, both RRF and peritoneal clearances should be monitored periodically.
  2. Until the actual equivalence of the peritoneal and renal components of clearance is characterized, the loss of RRF should be replaced with an equivalent or higher dose of peritoneal clearance.
  3. Anuric patients should be rigorously monitored with particular attention to nutrition and their dose adjusted to the practical maximum.

References:

  1. Maiorca R, Brunori G, Zubani R, Cancarini GC, Manili L, Camerini C, Movilli E, Pola A, d’Avolio G, Gelatti U. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients.  A longitudinal study. Nephrol Dial Transplant. 1995 Dec;10(12):2295-305. https://www.ncbi.nlm.nih.gov/pubmed/8808229
  2. Diaz-Buxo JA, Lowrie EG, Lew NL, et al.  Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis. 1999 Mar;33(3):523-34.https://www.ncbi.nlm.nih.gov/pubmed/10070917
  3. Szeto CC, Wong TYH, Leung CB, et al.  Importance of dialysis adequacy in mortality and morbidity of Chinese CAPD patients. Kidney Int. 2000 Jul;58(1):400-7  https://www.ncbi.nlm.nih.gov/pubmed/10886588
  4. Rocco M, Soucie JM, Pastan S, McClellan WM.  Peritoneal dialysis adequacy and risk of death. Kidney Int. 2000 Jul;58(1):44657. https://www.ncbi.nlm.nih.gov/pubmed/10886593
  5. Bargman JM, Thorpe KE, Churchill DN. The relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: A reanalysis of the CANUSA study. J Am Soc Nephrol. 2001 Oct;12(10):2158-62.https://www.ncbi.nlm.nih.gov/pubmed/11562415
  6. Termorshuizen F, Korevaar JC, Dekker FW, van Manen JG, Boeschoten EW, Krediet R. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: An analysis of the netherlands cooperative study on the adequacy of dialysis (Necosad)-2. Am J Kidney Dis. 2003 Jun;41(6):1293-302.https://www.ncbi.nlm.nih.gov/pubmed/11562415
  7. Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Dis. 2001 Jul;38(1):85-90. https://www.ncbi.nlm.nih.gov/pubmed/11431186
  8. Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT: Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol. 2004 Apr;15(4):1061-70.https://www.ncbi.nlm.nih.gov/pubmed/15034110
  9. Szeto CC, Wong TYH, Chow KM, et al.  Impact of dialysis adequacy on the mortality and morbidity of anuric Chinese patients receiving continuous ambulatory peritoneal dialysis.  J Am Soc Nephrol. 2001 Feb;12(2):355-60.https://www.ncbi.nlm.nih.gov/pubmed/11158226

P/N 101797-01 Rev A 06/2012